Biochemical and Pharmacologic Studies with Oncoloytic Barbituric Acid Derivatives Merbarone is a hybrid molecule, consisting of thiobarbituric acid conjoined to aniline in an amide linkage; the drug is curative of the L1210 leukemia. In last year's Annual Report it was documented that merbarone promptly arrested DNA synthesis in cultured L1210 cells. In the present year, the ability of merbarone to produce damage to DNA was examined. These studied used cultured L1210 cells as their principal tool. Exposure of these cells to an IC50 concentration of the drug for 16 hours resulted in a highly significant rate of single-strand breaks. These breaks did not, however, appear to be protein-associated. Approximately 24 hours were required for the repair of 50% of the SSB's. When merbarone was incubated with hepatic microsomes and NADPH, ESR signals suggestive of oxygen-centered radicals were generated. As a working hypothesis, it is suggested that such radicals may be mediating the DNA damage described here.